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Purpose: Human epidermal growth factor receptor 2 (HER2)-directed therapy improves local control among women with HER2-positive breast cancer. This retrospective analysis evaluates the safety and efficacy of radiation therapy (RT) among patients receiving adjuvant trastuzumab emtansine (T-DM1) or paclitaxel (T) plus trastuzumab (H) in the ATEMPT (Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab) trial; Translational Breast Cancer Research Consortium (TBCRC) 033.Methods and Materials: Patients with stage I HER2-positive breast cancer were randomized 3:1 to receive adjuvant T-DM1 or TH after mastectomy or breast-conserving surgery (BCS). Breast RT was required after BCS and permitted after mastectomy. Patients receiving T-DM1 began RT after 12 weeks of therapy and received RT concurrently with T-DM1. Patients receiving TH began RT after paclitaxel, but concurrent with trastuzumab. RT records were retrospectively reviewed to determine details of radiation delivery and acute RT-related toxicity.Results: Protocol therapy was initiated by 497 patients. Among the 299 BCS patients, 289 received whole breast RT (WBRT) and 10 partial breast. Among WBRT patients, 40.2% in the T-DM1 arm and 41.5% of TH patients received hypofractionated (≥2.5 Gy/fraction) RT. Eight mastectomy patients received RT, all conventional fractionation. Skin toxicity (grade ≥2) was seen in 33.9% of patients in the T-DM1 arm and 23.2% in the TH arm (P = .11). In conventionally fractionated WBRT patients, 44.7% had a grade ≥2 skin toxicity compared with 17.9% of patients receiving hypofractionation (P < .001). Five patients experienced pneumonitis after RT (T-DM1: n = 4, 1.0%; TH: n = 1, 0.9%). Three-year invasive disease-free survival was 97.8% for T-DM1 (95% confidence interval, 96.3-99.3) and 93.4% for TH (95% confidence interval, 88.7-98.2). Among the 18 invasive disease-free survival events, 7 were isolated locoregional recurrences (2, T-DM1; 5, TH).Conclusions: RT was well-tolerated when given concurrently with either T-DM1 or TH. Among BCS patients, hypofractionation resulted in lower grade ≥2 acute skin toxicity even with concurrent anti-HER2 therapy. Although follow-up was short, local recurrences were uncommon, attesting to the efficacy of HER2-directed therapy combined with RT. [ABSTRACT FROM AUTHOR]

Purpose: Patients with triple-negative breast cancer (TNBC) experience higher local-regional recurrence rates than those with luminal or HER2-positive tumors. This prospective, phase 1B trial was designed to assess the safety and to establish the maximum tolerated dose (MTD) of cisplatin with radiation therapy for women with early-stage TNBC.Methods and Materials: Eligible patients had stage II or III TNBC. Cisplatin was initiated at 10 mg/m2 intravenously once weekly during radiation and then escalated in a 3 + 3 design by 10 mg/m2 at each dose level until 40 mg/m2, or the MTD, was reached. Patients undergoing breast-conserving therapy (BCT) or mastectomy were accrued in separate parallel cohorts during dose escalation, followed by a 10-patient expansion at the MTD.Results: During 2013 to 2018, 55 patients were accrued. Four patients developed dose-limiting toxicity. In the BCT cohort, 1 patient receiving 40 mg/m2 developed tinnitus resulting in a cisplatin delay; therefore, this was the BCT cohort MTD. In the mastectomy cohort, 1 patient receiving 20 mg/m2 developed a grade 3 urinary infection, and 2 additional patients had dose-limiting toxicities at 40 mg/m2 (grade 3 neutropenia and grade 2 tinnitus), both resulting in cisplatin delay. Thus, 30 mg/m2 was the mastectomy cohort MTD. Median follow-up was 48.5 months. Three-year disease-free survival was 74.7% for the BCT cohort and 64.4% for the mastectomy cohort.Conclusions: Adjuvant radiation therapy with concurrent cisplatin is feasible with a recommended phase 2 dose of 30 mg/m2 and 40 mg/m2 intravenously weekly in mastectomy and BCT cohorts, respectively. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). Methods and Materials: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weekly × 12 weeks (60 mg/m2), or every 3 weeks × 4 cycles (135–175 mg/m2). Radiation fields and schedules were determined by the patient’s surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. Results: Weekly paclitaxel treatment at 60 mg/m2 per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135–175 mg/m2. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. Conclusions: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury. [Copyright &y& Elsevier]